Is BABAM2 p.Val287Leu (c.859G>T) pathogenic?

BABAM2 p.Val287Leu (c.859G>T) is classified Uncertain significance in BABAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: likely pathogenic (0.5701); Absent from gnomAD v4.1.

How common is BABAM2 p.Val287Leu (c.859G>T) in the general population?

BABAM2 p.Val287Leu (c.859G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BABAM2 p.Val287Leu (c.859G>T)?

AlphaMissense predicts likely pathogenic (score 0.5701) — an in-silico prediction, not a clinical call.

BABAM2 p.Val287Leu

c.859G>T · VCV3259709

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5701 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5701	likely pathogenic
REVEL	0.427	indeterminate
SaProt	LLR -6.72	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.8, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 444 kb · p 1.7e-05 · regional, not allelic
Overall
CADD	21.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BABAM2
Protein: p.Val287Leu
Coding: c.859G>T
MANE Select: NM_199191
Type: single nucleotide variant
Location: chr2:28244787 (GRCh38)
Gene constraint: LOEUF 0.753 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.76 · 13 PDB
Residue 287: the 'uev-like 2' region; a β-strand

Full BABAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BABAM2 p.Val287Met Uncertain significance ★ ⚠ same residue
BABAM2 c.1089-11028A>G Uncertain significance ★ same type
BABAM2 c.1089-11081G>A Uncertain significance ★ same type
BABAM2 c.1089-11108C>G Uncertain significance ★ same type
BABAM2 c.1089-11127G>A Uncertain significance ★ same type
BABAM2 c.1089-11144C>T Uncertain significance ★ same type
BABAM2 c.1089-11169C>G Uncertain significance ★ same type
BABAM2 p.Arg131Cys Uncertain significance ★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/babam2-p-val287leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown